The Qa-Tla region of murine chromosome 17 controls the expression of a group of cell surface antigens which serve as phenotypic markers of selected lymphocyte subpopulations and as determinants which elicit the generation of H-2 non restricted cytotoxic T lymphocytes (CTL). The aims of this proposal are to biochemically characterize the Qa-1 alloantigens and related Qa-Tla encoded molecules in an effort to elucidate the structural and genetic complexity of this region of the chromosome. A chemical investigation of these molecules should also be of value to our understanding of the evolutionary and functional relationship between the Qa-Tla alloantigens and the H-2 major transplantation antigens. In addition to the biochemical studies described, attempts will be made to generate monoclonal antibodies to Qa-1 determinants as well as other known or potentially new (undefined) Qa-Tla region molecules. The chemical analysis of Qa-1 and related structures will be approached using biochemical techniques which have been extremely successful in characterization of other cell surface molecules. Alloantisera to the Qa-1a and -1b allelic products are available, and I have found that these two antisera are effective in specifically immunoprecipitating glycoproteins of 46,000 MW. I plan to use these antisera (or monoclonal antibodies) to biochemically characterize the Qa-1 antigens by SDS-PAGE, isoelectric focusing, and 2-D gel systems. Subpopulations of resting and mitogen activated T and B lymphocytes will be examined for potential variations in the biochemical structure of Qa-1. Comparative peptide mapping techniques will be employed to assess the extent of polymorphism among the Qa-1 alleles. This technique will also be used to explore potential structural relationships between Qa-1 antigens and other chromosome 17 alloantigens of similar subunit structure. Additionally, NH2-terminal amino acid sequence analysis studies will be undertaken to search for structural homologies, which may not be apparent by peptide mapping, between Qa-Tla and the H-2 transplantation antigens.